Selection of resistant mutants of Citrobacter freundii by second and third-generation cephalosporins and imipenem.

Using a single-step selection procedure, resistant mutants could be obtained from three clinical isolates of Citrobacter freundii with two second-generation and four third-generation cephalosporins but not with imipenem. All mutants showed a drastically increased beta-lactamase activity and were cross-resistant to all the cephalosporins examined. Combinations of cloxacillin with the cephalosporins were markedly synergistic, suggesting the principal role of the cephalosporinase in the resistance of these mutants.